**15. EVA-3S**

262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4 years of follow-up was higher with stenting than with endarterectomy (11 1% vs. 6 2%, hazard ratio [HR] 1 97, 95% CI 1 06–3 67; p=0 03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2 00 (0 75–5 33; p=0 17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1 77 (1 03–3 02; p=0 04). For any stroke or death, the HR was 1 39 (0 96–2 00; p=0 08). The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis.[22]

p=0.006), Risks of any stroke (65 vs. 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs. seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of

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At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5 93, 95% CI 2 25–15 62; p=0 0003). In patients treated at a center with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12 20, 95% CI 4 53–32 84), whereas in those treated at a center with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy

which were fatal, compared with four, all non-fatal, in the endarterectomy group.[26]

group had new lesions on DWI (adjusted OR 2 70, 1 16–6 24; interaction p=0 019).[27]

previous procedures).[18]

**17. CREST trial**

larger trial trying to reach the truth.

These discordant results may be explained by the fact that the EVA-3S and SPACE studies differ from ours in numerous ways, including in the selection criteria (e.g., the EVA-3S and SPACE trials included neither patients with a high surgical risk nor asymptomatic patients), the rate of use of specific emboli-protection devices (in 92% of cases in the EVA-3S trial and 27% in the SPACE trial), and the experience level of the physician who placed the stent (in the EVA-3S trial, stents could be placed by physicians who had performed as few as five previous carotid-stent procedures or, if working under the direction of a tutor, no

The results of the previous studies were a major setback for stenting. They created a general belief among practicing physicians and neurologists that carotid artery stenting has only a limited role in the prevention of stroke. This set the stage ready for a more comprehensive

The CREST (Carotid Revascularization Endarterectomy vs. Stent Trial) was a multicenter trial supported by the National institute of health. The study includes symptomatic (>50% stenosis) and asymptomatic (>70% stenosis) patients. The CREST was probably the largest study on carotid revascularization and had the best design. Centers were required to have a team consisting of a neurologist, an interventionist, a surgeon, and a research coordinator. Patients could not be randomly assigned to a treatment group until the operators performing carotid artery stenting and carotid endarterectomy had been certified. Certification was achieved by 477 surgeons, whose clinical results were audited by means of a validated selection process documenting that they performed more than 12 procedures per year and that the rates of complications and death were less than 3% among asymptomatic patients and less than 5% among symptomatic patients. The 224 interventionists were certified after satisfactory evaluation of their endovascular experience, carotid-stenting results, participation in hands-

on training, and participation in a lead-in phase of training.[28]

In the same study, the rate of carotid restenosis of ≥50% or occlusion was significantly higher after CAS (12.5%) than after CEA (5.0%; time ratio, 0.16; 95% CI, 0.03–0.76; *P*=0.02). The rates of severe restenosis of ≥70% or occlusion were low and did not differ significantly between the 2 groups (3-year rates are 3.3% in the CAS group and 2.8% in the CEA group). Age at baseline was the only vascular risk factor significantly associated with carotid restenosis. Our study could not detect any effect of carotid restenosis on ipsilateral stroke.[23]

It was notable that the risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0 001) but not in the CEA group (p=0 534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2 7% (8/293) in patients who were 68 years old or younger and 10 8% (34/314) in older patients.[24]

In the first 120 days after randomization (ITT analysis), the primary outcome event occurred in 153/1725 patients in the CAS group (8.9%) compared with 99/1708 patients in the CEA group (5.8%, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20–1.95, p = 0.0006; absolute risk difference 3.2, 95% CI 1.4–4.9). Age was the only subgroup variable which significantly modified the treatment effect: in patients <70 years old (the median age), the 120-day stroke or death risk was 5.8% in CAS and 5.7% in CEA (RR 1.00, 0.68–1.47); in patients 70 years or older, there was an estimated two-fold increase in risk with CAS over CEA (12.0% vs. 5.9%, RR 2.04, 1.48–2.82, interaction p = 0.0053).[25]

Endarterectomy was safer in the short-term than stenting, because of an increased risk of stroke associated with stenting in patients over the age of 70 years. Stenting should be avoided in older patients, but may be as safe as endarterectomy in younger patients. Determination of the efficacy and ultimate balance between the two procedures requires further data on long-term stroke recurrence.[25]
